scholarly journals VIRAL DELIVERY USING SCAFFOLDS

2021 ◽  
Vol 20 (2) ◽  
pp. 19-30
Author(s):  
A. A. Laevskaya ◽  
V. V. Kosenchuk ◽  
S. I. Yakushov ◽  
P. S. Timashev ◽  
I. V. Ulasov
Keyword(s):  
Viral Vectors ◽  
Materials Science ◽  
Viral Vector ◽  
3D Models ◽  
Premature Aging ◽  
Biologically Active ◽  
Target Cells ◽  
Bioactive Polymers ◽  
Material Chemistry ◽  
Potential Benefits

In experimental oncology there are multiple approaches have been developed to target tumor cells. Many of them are based on scaffolds, a 3D models that mimics the structure of tissue in normal and pathophysiological state. It  is known that to deliver a viral load to target cells, cells-carriers undergo limited differentiation, and premature aging. Since viral agents require cells to be in specific proliferative state, the delivery of the virus to the target cell is the main goal of the functional framework such as scaffold. Over decade, multiple studies demonstrate the production of scaffolds using matrigel, polyalacinic acid, poly-lactide-co-glycolide, vinyl stilbens, or bioactive polymers. Our review will describe the potential benefits of delivering the viral vector using 3D scaffolds for virus-mediated expression of biologically active substances that prevent angiogenesis, neoplasm proliferation, or, conversely, stimulate wound healing. 3D materials such as hydrogels and scaffolds are among the key innovations in the field of material chemistry. Moreover, viral vectors provide specific delivery of genes to target cells. However, the immunogenicity of a viral capsid consisting of viral proteins hinders the clinical use of such vectors widely. These limitations can be surmounted by using scaffolds. Therefore, our review might interest researchers working in the fields of chemistry, materials science and natural sciences, as well as in the field of bioengineering and medical technologies.

Nanotechnology for Gene Delivery to the Eye

2009 ◽  
Vol 03 (01) ◽  
pp. 7 ◽  
Author(s):  
Swita R Singh ◽  
Uday B Kompella ◽  
◽  
Keyword(s):  
Gene Delivery ◽  
Enzymatic Degradation ◽  
Viral Vectors ◽  
Viral Vector ◽  
Target Cells ◽  
Loading Capacity ◽  
Adeno Associated Virus ◽  
Complementary Dna ◽  
Privileged Status ◽  
Potential Applications

The relatively immune-privileged status of the eye makes it an interesting target for gene delivery. Gene delivery to the eye using viral vectors via subretinal and intravitreal injections has been extensively investigated. Recently, the safety of recombinant adeno-associated virus vector expressing RPE65 complementary DNA (cDNA) in a limited clinical trial of three patients has also been reported. Nanotechnology-based non-viral vectors offer the advantages of safety and flexibility in terms of loading capacity and delivery system design compared with viral vectors. An ideal non-viral vector should be non-toxic, efficiently taken up into the target cells and conducive to gene expression, and should protect the gene against enzymatic degradation. Multiple kinds of nanotechnology-based non-viral vectors have been investigated for potential applications for gene delivery to the eye, namely nanoplexes, dendrimers, micelles, nanoparticles and liposomes. This article summarises and discusses key advances in the application of nanotechnology for gene delivery to the eye.

scholarly journals Engineering multiple levels of specificity in an RNA viral vector

2020 ◽  
Author(s):  
Xiaojing J. Gao ◽  
Lucy S. Chong ◽  
Michaela H. Ince ◽  
Matthew S. Kim ◽  
Michael B. Elowitz
Keyword(s):  
Viral Vectors ◽  
Viral Vector ◽  
Cell Types ◽  
Model System ◽  
Surface Proteins ◽  
Target Cells ◽  
Specific Cell ◽  
Intracellular Protein ◽  
Cell Surface Proteins ◽  
Multiple Levels

AbstractSynthetic molecular circuits could provide powerful therapeutic capabilities, but delivering them to specific cell types and controlling them remains challenging. An ideal “smart” viral delivery system would enable controlled release of viral vectors from “sender” cells, conditional entry into target cells based on cell-surface proteins, conditional replication specifically in target cells based on their intracellular protein content, and an evolutionarily robust system that allows viral elimination with drugs. Here, combining diverse technologies and components, including pseudotyping, engineered bridge proteins, degrons, and proteases, we demonstrate each of these control modes in a model system based on the rabies virus. This work shows how viral and protein engineering can enable delivery systems with multiple levels of control to maximize therapeutic specificity.

Sustained phenotypic correction of canine hemophilia A using an adeno-associated viral vector

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2031-2037 ◽  
Author(s):  
Ciaran D. Scallan ◽  
David Lillicrap ◽  
Haiyan Jiang ◽  
Xiaobing Qian ◽  
Susannah L. Patarroyo-White ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Hemophilia A ◽  
Viral Vector ◽  
Regulatory Elements ◽  
Canine Model ◽  
Biologically Active ◽  
Activity Levels ◽  
Major Disadvantage ◽  
Fviii Activity ◽  
Efficient Delivery

Abstract Gene therapy for hemophilia A requires efficient delivery of the factor VIII gene and sustained protein expression at circulating levels of at least 1% to 2% of normal. Adeno-associated viral type 2 (AAV2) vectors have a number of advantages over other viral vectors, including an excellent safety profile and persistent gene expression. However, a major disadvantage is their small packaging capacity, which has hampered their use in treating diseases such as hemophilia A, cystic fibrosis, and muscular dystrophy, which are caused by mutations in large genes. Here we demonstrate that this can be overcome by using small regulatory elements to drive expression of a B-domain–deleted form of FVIII. The use of this vector for hepatic gene transfer in a canine model of hemophilia A resulted in the sustained (> 14 months) expression of biologically active FVIII. FVIII activity levels of 2% to 4% were achieved. These levels correlated with a partial correction in the whole-blood clotting time and cuticle bleeding time. In addition, immunoprecipitation analysis demonstrated the expression of canine FVIII of the predicted size in the plasma of injected animals. These data support the use of AAV2 vectors in human clinical trials to treat hemophilia A patients.

Rationale of Using Conventional Sol-Gel Derived SiO2 for Delivery of Biologically Active Agents

2008 ◽  
Vol 377 ◽  
pp. 195-210 ◽  
Author(s):  
Mika Jokinen ◽  
Mika Koskinen ◽  
Sami Areva
Keyword(s):  
Viral Vectors ◽  
Large Scale ◽  
Materials Science ◽  
Sol Gel ◽  
Extreme Case ◽  
Biologically Active ◽  
In Vitro Dissolution ◽  
Highly Sensitive ◽  
Hierarchical Pore

Progress in the research of mesoporous materials, hierarchical pore structures, chemical modification of surfaces, nanoparticle processing and hybrid materials is important and it provides new and interesting functional properties for silica structures. However, this has also left the conventional, alkoxy-based sol-gel derived silica in the shadow, although it has a lot of non-utilized potential, especially in the delivery and/or encapsulation of sensitive biologically active agents like viral vectors, proteins, nucleic acids and cells. The potential lies in the versatile possibilities to adjust the structure by using alkoxides as precursors and in the proper use of water in different steps of the processing. The conventional, alkoxy-based sol-gel silica structure can be processed so that it results in largely variable biodegradation rates, biodegradation-controlled release of encapsulated agents and beneficial environment even for highly sensitive agents. These kinds of silica structures contain more or less water and hence, they are more or less labile from the traditional viewpoint of materials science. In extreme case they could be called “unfinished silica”. The aim of this paper is to discuss how the biodegradation rate of these kinds of silica materials can be adjusted on a large scale and how this is related to a rather narrow scale adjustment of in vitro dissolution rate of silica, how the unfinished silica structures can be controlled and their properties adjusted, how they can be utilized in the delivery of biologically active agents, and what the potential problems to be solved are.

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Large Scale ◽  
Transfection Efficiency ◽  
Cationic Lipids ◽  
Target Cells ◽  
Scale Production ◽  
Stepwise Development ◽  
Chimeric Peptides

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

scholarly journals VipariNama: RNA viral vectors to rapidly elucidate the relationship between gene expression and phenotype

2021 ◽  
Author(s):  
Arjun Khakhar ◽  
Cecily Wang ◽  
Ryan Swanson ◽  
Sydney Stokke ◽  
Furva Rizvi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Viral Vectors ◽  
Viral Vector ◽  
Tobacco Rattle Virus ◽  
Plant Size ◽  
Great Promise ◽  
Attractive Alternative ◽  
Gibberellin Biosynthesis ◽  
In Planta

Abstract Synthetic transcription factors have great promise as tools to help elucidate relationships between gene expression and phenotype by allowing tunable alterations of gene expression without genomic alterations of the loci being studied. However, the years-long timescales, high cost, and technical skill associated with plant transformation have limited their use. In this work we developed a technology called VipariNama (ViN) in which vectors based on the Tobacco Rattle Virus (TRV) are used to rapidly deploy Cas9-based synthetic transcription factors and reprogram gene expression in planta. We demonstrate that ViN vectors can implement activation or repression of multiple genes systemically and persistently over several weeks in Nicotiana benthamiana, Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum). By exploring strategies including RNA scaffolding, viral vector ensembles, and viral engineering, we describe how the flexibility and efficacy of regulation can be improved. We also show how this transcriptional reprogramming can create predictable changes to metabolic phenotypes, such as gibberellin biosynthesis in N. benthamiana and anthocyanin accumulation in Arabidopsis, as well as developmental phenotypes, such as plant size in N. benthamiana, Arabidopsis, and tomato. These results demonstrate how ViN vector-based reprogramming of different aspects of gibberellin signaling can be used to engineer plant size in a range of plant species in a matter of weeks. In summary, VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

scholarly journals How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

2021 ◽  
Vol 22 (14) ◽  
pp. 7545
Author(s):  
Myriam Sainz-Ramos ◽  
Idoia Gallego ◽  
Ilia Villate-Beitia ◽  
Jon Zarate ◽  
Iván Maldonado ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Practice ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Vector ◽  
Clinical Success ◽  
Genetic Material ◽  
Viral Gene ◽  
Promising Alternative ◽  
Vector Systems

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

Collagenase secretion accompanying changes in cell shape occurs only in the presence of a biologically active cytokine

1989 ◽  
Vol 92 (3) ◽  
pp. 473-485
Author(s):  
I. Kuter ◽  
B. Johnson-Wint ◽  
N. Beaupre ◽  
J. Gross
Keyword(s):  
Cell Cultures ◽  
Cell Shape ◽  
Cell Function ◽  
Shape Change ◽  
Biologically Active ◽  
Target Cells ◽  
Mixed Cell ◽  
Cell Shape Change ◽  
Cell Shape Changes ◽  
Shape Changes

We have investigated the relationship between collagenase production, cell shape and stimulatory factors in cell culture. In a homogeneous culture of primary rabbit corneal stromal cells, shape change induced by a variety of agents was not effective in stimulating collagenase secretion. Only in the presence of a biologically active cytokine or phorbol myristate acetate was a correlation seen between changes in cell shape (induced by a second agent) and collagenase secretion by these primary cells. Cell shape changes were not, however, necessary for collagenase secretion, since certain concentrations of endotoxin or lactalbumin hydrolysate effected secretion of the enzyme in the absence of morphological changes. With passaged cells or mixed cell cultures, where cell shape change did correlate with collagenase secretion without the addition of an exogenous agent, the production of an effective cytokine (autocrine or paracrine) was demonstrated. Thus cell shape change seems to be neither universally necessary nor sufficient for the stimulation of collagenase secretion. It is proposed that the function of cytokines may be more immediately related to gene expression in this system than is change in the shape of the cell. The hypothesis is presented that cell shape changes may render the target cells receptive to cytokines, perhaps by replacing the need for a natural cytokine cofactor. It is also demonstrated here that the use of passaged cells, mixed cell cultures containing endogenous cytokine-secreting cells or tissue culture additives can profoundly affect the interpretation of the effect of various agents on collagenase secretion, and may lead to observations that are not directly relevant to cell function in vivo.

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